Frequency of FGF14 intronic GAA repeat expansion in patients with multiple system atrophy and undiagnosed ataxia in the Japanese population

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic nervous system dysfunction and cerebellar ataxia or parkinsonism. Recently, expanded GAA repeats (≥250 repeat units) in intron 1 of FGF14 have been shown to be responsible for spinocerebellar ataxia type 27B (SCA27B), a late-onset ataxia with an autosomal dominant inheritance. Patients with SCA27B may also exhibit autonomic nervous system dysfunction, potentially overlapping with the clinical presentations of MSA patients. In this study, to explore the possible involvement of expanded GAA repeats in MSA, we investigated the frequencies of expanded GAA repeats in FGF14 in 548 patients with MSA, 476 patients with undiagnosed ataxia, and 455 healthy individuals. To fully characterize the structures of the expanded GAA repeats, long-range PCR products suggesting the expansion of GAA repeats were further analyzed using a long-read sequencer. Of the 548 Japanese MSA patients, we identified one MSA patient (0.2%) carrying an expanded repeat with (GAA)<sub>≥250</sub>. Among the 476 individuals with undiagnosed ataxia, (GAA)<sub>≥250</sub> was observed in six (1.3%); this frequency was higher than that in healthy individuals (0.2%). The clinical characteristics of the MSA patient with (GAA)<sub>≥250</sub> were consistent with those of MSA, but not with SCA27B. Further research is warranted to explore the possibility of the potential association of expanded GAA repeats in FGF14 with MSA.

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Journal
European Journal of Human Genetics
Published
2024-11-27
DOI
https://doi.org/10.1038/s41431-024-01743-3
Citations
6
Primary Topic
Genetic Neurodegenerative Diseases
Type
article
Field-Weighted Citation Impact
1.61
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article

Frequency of FGF14 intronic GAA repeat expansion in patients with multiple system atrophy and undiagnosed ataxia in the Japanese population

Ichiro Yabe, Hiroyuki Ishiura, Satoshi Kuwabara, Masaaki Matsushima et al.
6 citations
European Journal of Human Genetics
Genetic Neurodegenerative Diseases
1.61
article

Frequency of FGF14 intronic GAA repeat expansion in patients with multiple system atrophy and undiagnosed ataxia in the Japanese population

Ichiro Yabe, Hiroyuki Ishiura, Satoshi Kuwabara, Masaaki Matsushima, Tomohiko Ishihara, Tadashi Adachi, Ayaka Chikada, Yuji Takahashi, Jun‐ichi Kira, Tetsuya Nagata, Masahisa Katsuno, Yoichiro Nishida, Ritsuko Hanajima, Yoshitaka Yamanaka, Jun Mitsui, Keiko Higashi, Shinichi Morishita, Atsuhiko Sugiyama, Shoji Tsuji, Toru Yamashita, Kinya Ishikawa, Hiroshi Takashima, Kenta Orimo, Yuta Suzuki, Kōji Abe, Tomoyuki Ishimoto, Nobukatsu Sawamoto, Masayoshi Tada, Yusuke Sakato, Toshiyuki Kakumoto, Osamu Onodera, Kokoro Ozaki, Ryōsuke Takahashi, Takashi Matsukawa, Kazuhiro Hara, Yasuhiro Watanabe, Hiroshi Takigawa, Hidehiro Mizusawa, Katsuhisa Ogata, Taro Ishiguro, Tatsushi Toda
article en
6 citations

Abstract

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic nervous system dysfunction and cerebellar ataxia or parkinsonism. Recently, expanded GAA repeats (≥250 repeat units) in intron 1 of FGF14 have been shown to be responsible for spinocerebellar ataxia type 27B (SCA27B), a late-onset ataxia with an autosomal dominant inheritance. Patients with SCA27B may also exhibit autonomic nervous system dysfunction, potentially overlapping with the clinical presentations of MSA patients. In this study, to explore the possible involvement of expanded GAA repeats in MSA, we investigated the frequencies of expanded GAA repeats in FGF14 in 548 patients with MSA, 476 patients with undiagnosed ataxia, and 455 healthy individuals. To fully characterize the structures of the expanded GAA repeats, long-range PCR products suggesting the expansion of GAA repeats were further analyzed using a long-read sequencer. Of the 548 Japanese MSA patients, we identified one MSA patient (0.2%) carrying an expanded repeat with (GAA)<sub>≥250</sub>. Among the 476 individuals with undiagnosed ataxia, (GAA)<sub>≥250</sub> was observed in six (1.3%); this frequency was higher than that in healthy individuals (0.2%). The clinical characteristics of the MSA patient with (GAA)<sub>≥250</sub> were consistent with those of MSA, but not with SCA27B. Further research is warranted to explore the possibility of the potential association of expanded GAA repeats in FGF14 with MSA.

European Journal of Human GeneticsVol. 33(3)
Kagoshima University (JP), Tokyo Medical and Dental University (JP), Kyushu University (JP), Chiba University (JP), Okayama University (JP), Hokkaido University (JP), Kyoto University (JP), National Center of Neurology and Psychiatry (JP), National Hospital Organization (JP), Tottori University (JP), Nagoya University (JP), Niigata University (JP), The University of Tokyo (JP), International University of Health and Welfare (JP)
Good health and well-being
Openalex Percentile: Top 17%
Genetic Neurodegenerative Diseases
1.61
DOIOpen Access PDFOpenAlex
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